Resveratrol, Found in Red Wine, Worsens MS-Like Symptoms and Neuropathology in Mice

Researchers discourage supplemental use by
patients with multiple sclerosis, according to report in The American Journal
of Pathology

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Philadelphia, PA, October 1, 2013

Resveratrol, a naturally occurring polyphenol compound
produced by the skin of red grapes and peanuts, and found in red wine, has been
touted as a beneficial supplement due to its anti-inflammatory and antioxidant
properties. This has been supported by some experimental studies, whereas
others suggest a lack of benefit. A new study using two multiple sclerosis (MS)
models published in The American Journal
of Pathology has found that resveratrol actually worsened MS-like
neuropathology and inflammation and had no neuroprotective effects.

"Resveratrol may have detrimental effects in some disease
conditions and should be discouraged for supplemental use by MS patients
pending further research," says lead investigator Ikuo Tsunoda, MD, PhD, Assistant
Professor in the Department of Microbiology and Immunology, Center for
Molecular & Tumor Virology of the Louisiana State University Health
Sciences Center, Shreveport, LA.

Investigators (Fumitaka Sato, PhD, et al) tested
resveratrol in autoimmune and viral models of MS. In the autoimmune model,
experimental autoimmune encephalomyelitis (EAE) was induced in 6-week-old mice
using myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. Mice
were fed either a control diet or a diet containing resveratrol for 2 months or
only during the early (days -1 to 8) or the late (days 14 to 23) phases of EAE.
Around 12 days after MOG sensitization, all groups started to develop clinical
signs, such as tail and hind limb paralysis, and the symptoms worsened and
peaked by 3 weeks. After 5 weeks, mice fed the control diet showed either
complete recovery or mild paralysis, but all three groups fed resveratrol
exhibited severe and lasting EAE without remission.

Spinal cord neuropathology showed higher pathology scores
in demyelination, meningitis, perivascular cuffing (inflammation), and overall
pathology in mice that had been given resveratrol during the early phase compared
with mice fed a control diet, whereas mice treated with resveratrol during the
entire treatment period had significantly higher pathology scores in meningitis
and overall pathology than controls. Groups did not differ in brain pathology
scores.

Although it has been suggested that resveratrol has
anti-inflammatory properties, in this study resveratrol did not suppress
autoimmune responses as measured by levels of MOG35-55-specific
lymphoproliferative responses and pro-inflammatory cytokine production.

To see whether resveratrol had anti-viral properties, as
has been reported, 5-week-old mice were infected intracerebrally with the
Daniels (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) to induce
TMEV-induced demyelinating disease (TMEV-IDD). The mice were fed either a
control diet or one containing resveratrol from days 35 to 48 (the chronic phase).
Similar to the findings from the EAE model, mice treated with resveratrol
developed significantly more severe TMEV-IDD compared with the controls.
Another study using the GDVII strain of TMEV to see whether resveratrol could
suppress neurodegeneration caused by direct viral infection, not by
immunopathology, found that resveratrol had no neuroprotective activity against
the virus.

"Resveratrol did not show anti-viral effects in TMEV
infection," says Dr. Tsunoda, although he notes that resveratrol has been shown
by others to have anti-viral effects on some viruses related to MS, such as
herpes simplex virus and Epstein-Barr virus.

To explain their findings, the authors suggest that
resveratrol's vasodilating effects via endothelial cells might enhance
infiltration of inflammatory cells into the central nervous system, which in
turn might play a key role in the pathogenesis of MS.

The degree to which resveratrol exacerbated demyelination
and inflammation surprised the research team. "Our findings illustrate that
caution should be exercised for potential therapeutic application of
resveratrol in human inflammatory demyelination diseases, including MS," says
Dr. Tsunoda.

Full text of the article is available to credentialed
journalists upon request; contact Eileen Leahy at +1 732 238 3628 or ajpmedia@elsevier.com. Journalists
wishing to interview the authors should contact Ikuo Tsunoda, MD, PhD, at +1
318 675 5757 or itsuno@lsuhsc.edu, or
Sally Croom, Executive Director, Communications and Public Affairs, Louisiana
State University Health Sciences Center, at scroom@lsuhsc.edu.

About The American Journal Of PathologyThe American
Journal of Pathology (http://ajp.amjpathol.org),
official journal of the American Society for Investigative Pathology, seeks to
publish high-quality, original papers on the cellular and molecular biology of
disease. The editors accept manuscripts that advance basic and translational
knowledge of the pathogenesis, classification, diagnosis, and mechanisms of
disease, without preference for a specific analytic method. High priority is
given to studies on human disease and relevant experimental models using
cellular, molecular, animal, biological, chemical, and immunological approaches
in conjunction with morphology.

The leading global forum for reporting quality original research on
cellular and molecular mechanisms of disease, The American Journal of
Pathology is the most highly cited journal in Pathology – over 38,000 cites
in 2012 – with an Impact Factor of 4.522 and Eigenfactor of 0.07599 according
to the 2012 Journal Citation Reports®,
Thomson Reuters, and an H index of 181 according to the 2011 SCImago Journal and Country Rank.

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